tbuckley/cabot-search huggingface dataset:
P-188 Transgelin/PARP1 regulates colorectal cancer metastasis through Rho GTPase pathway
Authors: Z. Ye, Y. Lin
Journal: Annals of Oncology (2022)

Our previous studies showed that transgelin may promoted the migration of HT29 and HCT116 colon cancer cells through nuclear translocation. Proteomics analysis demonstrated that transgelin interacted with 297 proteins, while the gene expression profile showed that TAGLN affected the expression of 256 downstream genes. Bioinformatics analysis identified 7 key genes, the Rho GTPase signaling pathway as the key pathway, and suggested that PARP1 may participate in the regulation of the key genes with transgelin. This study aims to verify the interaction between PARP1 and transgelin, and explore the mechanism of transgelin/PARP1 in regulating the metastasis of colorectal cancer. Co-immunoprecipitation and immunoblotting were used to verify the interaction between PARP1 and transgelin. The expression of PARP1 in colorectal cancer and non-cancerous tissues were analyzed with the mRNA data from GEO microarrays and TCGA database, and were also examined with a tissue microarray by immunohistochemistry. Kaplan-Meier Analysis was performed to analyze the influence of PARP1 expression on overall survival. We then explored the nuclear localization of transgelin in siRNA-mediated knockdown of PARP1 in colon cancer cells by immunoblotting and immunofluorescence. The proliferation, migration and invasion of PARP1-knockdown SW480 and RKO cells were detected by CCK8, wound healing and transwell invasion assays. An expression plasmid containing RAC1 which was one of the key genes identified from the TAGLN-overexpression cDNA microarray analysis, and also a key member of the Rho GTPase family was constructed. This plasmid was co-transfected with PARP1-siRNA into SW480 and RKO cells to replenish the expression of RAC1. The proliferation, migration and invasion assays of the co-transfected colon cancer cells were also performed. Immunoprecipitation and immunoblotting showed that PARP1 interacted with transgelin in HCT116 cells. The expression of PARP1 in colon cancer was increased as compared to the non-tumor samples p < 0.05). The expression of PARP1 was correlated with disease-free survival (p < 0.05) and overall survival p < 0.05. Knockdown of PARP1 reduced the nuclear transgelin in RKO and SW480 cells, and simultaneously decreased the proliferation migration and invasion of colon cancer cells, respectively. Overexpression of TAGLN led to increased expression of RAC1, while knockdown of PARP1 resulted in reduced expression of RAC1 in colon cancer cells. While the PARP1-knockdown cells were re-introduced with RAC1 expression, their proliferation migration and invasion ability were re-gained as compared to the control groups. Transgelin interacted with PARP1 in HCT116 cells. PARP1 was an adverse prognostic marker in colorectal cancer and participated in the nuclear translocation of transgelin. Transgelin / PARP1 may regulate the metastasis of colorectal cancer through RAC1 of the Rho GTPase signaling pathway.
LBA SO-34 Impact of BRAF-V600E mutation on immunologic characteristics of the tumor microenvironment (TME) and associated genomic alterations in patients with microsatellite instability-high (MSI-H) or mismatch-repair–deficient (dMMR) colorectal cancer (CRC)
Authors: M. Salem, S. Kopetz, S. El-Refai, J. Tabernero, F. Sinicrope, J. Tie, T. George, E. Van Cutsem, E. Mauer, S. Lonardi, T. André, M. Overman, D. Foureau
Journal: Annals of Oncology (2022)
P-155 Adjuvant therapy (AT) in patients (pts) with radically resected ampullary adenocarcinoma (AA): A monocentric retrospective analysis
Authors: D. Barone, M. Maratta, M. Bensi, G. Quero, C. Bagalà, C. Fiorillo, B. Di Stefano, V. Beccia, A. Spring, E. Gurreri, F. Monaca, M. Chiaravalli, S. Alfieri, G. Tortora, L. Salvatore
Journal: Annals of Oncology (2022)
SARS-CoV-2-induced senescence as a potential therapeutic target
Authors: Mary Denholm, Robert C. Rintoul, Daniel Muñoz-Espín
Journal: European Respiratory Journal (2022)

The global COVID-19 pandemic has caused major morbidity, mortality, and socioeconomic disruption on an individual and collective level. Over six million COVID-related deaths have been reported, with total case numbers now well over 500 million worldwide [1]. Whilst the prompt and efficient design of effective vaccines has restored varying degrees of normal activity to some parts of world, the effects of the pandemic will be long in duration and far-reaching.
P-21 Molecular subtypes (profile) of colorectal cancer and their correlation with clinical and pathological profile in a tertiary care centre in India
Authors: S. Joga, S. Goyal, A. Mehta, M. Sharma, V. Koyyala, D. Doval, P. Goyal, C. Aggarwal, None M. swamy, A.B. Patel, S. Nathani, M. Suryavanshi, S. Narayan, S. Soni, A. Jain, P. Redhu
Journal: Annals of Oncology (2022)
P-216 Serum levels of HMGB1 might have a predictive role for neoadjuvant radiotherapy combined with chemotherapy in rectal cancer patients
Authors: T. Radeva-Petkova, E. Encheva, G. Mihaylova, D. Palamudova, S. Bilyukova, T. Gugleva, E. Dimitrova, N. Tsonev, M. Radanova
Journal: Annals of Oncology (2022)
Letter to the Editor: Some reflection on the research related to METTL1 promoting radiotherapy resistance in hepatocellular carcinoma
Authors: Fan Yang, Shi‐Tao Jiang, Yong‐Chang Zheng
Journal: Hepatology (2022)

1 Department of Liver Surgery, Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina *Correspondence Yong‐Chang Zheng, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Email: [email protected]
Underwater hybrid endoscopic mucosal resection: a valid option for selected lesions
Authors: Mariana Figueiredo, Clara Yzet, Marianna Milashka, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2022)

Hybrid endoscopic mucosal resection (H-EMR) has been described as a valid alternative to traditional EMR. This technique involves an initial submucosal injection, followed by a circumferential incision and, finally, the resection of the central tissue with a snare [1]. This strategy can be applied to lesions under 20 mm in diameter, and allows the visualization and inclusion of the whole lesion, with certainty of complete en bloc resection [2]. However, H-EMR can be challenging to perform in nonlifting and difficult-to-access lesions. The underwater H-EMR technique has the potential to overcome this limitation.
Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy
Authors: Zekun Li, Yongchun Pan, Shiyu Du, Yayao Li, Chao Chen, Hongxiu Song, Yueyao Wu, Xiaowei Luan, Qin Xu, Xiaoxiang Guan, Yujun Song, Xin Han
Journal: Acta Pharmaceutica Sinica B (2022)

Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO
P-43 Correlation of mesothelin expression with recurrence in colorectal cancer (CRC) patients
Authors: M. Malla, J. Fuqua, D. Olevian, J. Avalon, C. Wakefield, None J. Karakiozis, B. Patel, B. Boone, C. Schmidt, S. Wen, Y. Agazie, L. Hazelhurst, R. Goldberg
Journal: Annals of Oncology (2022)
How to reduce the ecological impact of gastric peroral endoscopic myotomy: a small effort for the environment
Authors: Mariana Figueiredo, Clara Yzet, Daniel Grinberg, Thomas Lambin, Pierre-Jean Cottinet, Jérôme Rivory, Mathieu Pioche
Journal: Endoscopy (2022)

It is already common knowledge that endoscopic procedures are responsible for the production of large amounts of waste, mostly owing to the usage of a high number of disposable instruments [1]. Gastric peroral endoscopic myotomy (G-POEM) is a well-known procedure used for the treatment of refractory gastroparesis [2]. Like most submucosal endoscopic procedures, this technique requires the injection of a premixed methylene blue/glycerol solution into the submucosa, in order to raise a mucosal bleb and create the space to make a safe mucosal cut. This step is usually performed with a routine single-use sclerotherapy needle [2]; however, a DualKnife could also be used for the same purpose, allowing the use of one disposable injection needle to be spared.
P-174 OPTIMISE: Optimization of treatment selection and follow-up in oligometastatic colorectal cancer – a ctDNA-guided phase II randomized approach with a run-in feasibility part
Authors: K. Spindler, L. Callesen, R. Andersen, N. Pallisgaard, S. Kramer, S. Schlander, S. Rafaelsen, A. Boysen, L. Jensen, A. Jakobsen, T. Hansen
Journal: Annals of Oncology (2022)
P-147 Sensitization of pancreatic and colorectal cancer to radiotherapy, chemotherapy, and immune checkpoint inhibitors by newly developed proprotein convertase inhibitors
Authors: A. François, F. Soulet, L. Bouton, C. Porcheron, J. Descarpentrie, G. Desolneux, S. Evrard, S. Pernot, A. Khatib
Journal: Annals of Oncology (2022)

The pancreatic ductal adenocarcinoma (PDAC) has a bad prognosis with delayed diagnosis that significantly impedes the use of therapeutic resection. Similarly, colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place in the liver. A main reason for this situation is the already resistant or newly resistant tumors to all conventional current therapies. Here, we report the re-sensitization of PDAC and CRC cells to chemotherapy, radiotherapy and/or immune checkpoint inhibitors by the newly developed inhibitors that target the activity of the proprotein convertases, enzymes involved in the biological activation/maturation of various protein precursors crucial for the malignant phenotype of PDAC and CRC tumors. The in vitro studies include T-cell activation assay performed with plate-bound anti-CD3, qRT-PCR assay and immunocytochemistry for the analysis of the proprotein convertases expression in human cells and tissues. Flow cytometry analysis was performed on single cell suspension of hPBMCs and T cells to analyze PD-1 expression. The activity of the proprotein convertase was assessed by the evaluation of the enzymes' ability to digest the universal PC substrate, the fluorogenic peptide pERTKR-MCA. The analysis of the seven known PC family members, namely, Furin, PC1, PC2, PC4, PACE4, PC5 and PC7, revealed their presence with predominant expression of Furin in PDAC and CRC tissues while compared to non-cancerous tissues from the same patients that associated alteration of the epithelial structure with highly spread expression of Furin all over the tumors. Using computer-aided virtual screening and repurposing approved drug strategies we identify small molecules and repurpose approved drugs against Furin, the only convertase with published crystallographic structure. We generated a collection of 2082 small molecules with 15 molecules identified having an inhibitory Furin activity. Using human cancer organoids in the presence of some of these molecules, the latter were more sensitive to radiotherapy, Gemcitabine and/or 5-fluorouracil. Treatment of activated T cells or PBMCs with these inhibitors repressed significantly PD-1 expression. In preclinical studies using syngeneic mice, 5 molecules were found to significantly reduce tumor progression that associated enhanced survival and sensitivity to radiotherapy of the tumor cells-inoculated mice. The tumor regression was associated with enhanced T cells infiltration in the developed tumors. These findings suggest the potential efficacy of Furin inhibitors in the sensitization of pancreatic and metastatic colon tumors to drug resistance that may contribute to the development of efficient therapeutic strategies and to improve the prognosis of patients with these cancers.
P-148 The impact of second-line treatment after fist-line cisplatin plus gemcitabine in advanced biliary tract cancers: A mono-institutional retrospective study
Authors: E. Gurreri, M. Chiaravalli, M. Bensi, C. Bagalà, B. Di Stefano, V. Beccia, A. Spring, F. Monaca, D. Barone, M. Maratta, G. Tortora, L. Salvatore
Journal: Annals of Oncology (2022)
Facts and Hopes in Immunotherapy of Pancreatic Cancer
Authors: Bruno Bockorny, Joseph E. Grossman, Manuel Hidalgo
Journal: Clinical Cancer Research (2022)

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains one of the most challenging cancers to treat. For patients with advanced and metastatic disease, chemotherapy has yielded only modest incremental benefits, which are not durable. Immunotherapy has revolutionized the treatment of other solid tumors by leading to cures where none existed only a decade ago, yet it has made few inroads with PDAC. A host of trials with promising preclinical data have failed, except for in a small minority of patients with selected biomarkers. There is, however, a glimmer of hope, which we seek to cultivate. In this review, we discuss recent advances in the understanding of the uniquely immunosuppressive tumor microenvironment (TME) in PDAC, learnings from completed trials of checkpoint inhibitors, TME modifiers, cellular and vaccine therapies, oncolytic viruses, and other novel approaches. We go on to discuss our expectations for improved preclinical models of immunotherapy in PDAC, new approaches to modifying the TME including the myeloid compartment, and emerging biomarkers to better select patients who may benefit from immunotherapy. We also discuss improvements in clinical trial design specific to immunotherapy that will help us better measure success when we find it. Finally, we discuss the urgent imperative to better design and execute bold, but rational, combination trials of novel agents designed to cure patients with PDAC.
An observational study to determine the relationship between cough frequency and markers of inflammation in severe asthma
Authors: Joshua Holmes, Lorcan P.A. McGarvey, Surinder S. Birring, Hannah Fletcher, Liam G. Heaney
Journal: European Respiratory Journal (2022)

The relationship between objectively measured cough and type 2 (T2) biomarkers and other measures of asthma control and severity is poorly understood. The objective of this study was to assess the relationship between objective and subjective cough measurement tools and clinical biomarkers of asthma.Patients with severe asthma and mild-to-moderate asthma completed validated asthma and cough-related measurement tools (including ambulatory cough monitoring) and measurement of spirometry and T2 biomarkers (exhaled nitric oxide fraction (FENO) and peripheral blood eosinophil count). Patients were classified according to T2 status based on T2-low (FENO <20 ppb and peripheral blood eosinophils <150 cells·µL-1), T2-intermediate (FENO ≥20 ppb or peripheral blood eosinophils ≥150 cells·µL-1) or T2-high (FENO ≥20 ppb and peripheral blood eosinophils ≥150 cells·µL-1).61 patients completed the study measurements (42 severe asthma and 19 mild-to-moderate asthma). Patients with severe asthma had higher rates of cough than those with mild-to-moderate asthma in terms of total 24-h cough counts (geometric mean±sd 170.3±2.7 versus 60.8±4.1; p=0.002) and cough frequency (geometric mean±sd 7.1±2.7 versus 2.5±4.1 coughs·h-1; p=0.002). T2-low patients with severe asthma had significantly lower 24-h cough frequency compared with T2-intermediate and T2-high patients.In patients with low biomarkers of T2 inflammation, cough frequency measurements were not elevated, suggesting that the mechanism for cough in asthma is underlying T2 eosinophilic inflammation and the logical first step for treating cough in asthma may be to achieve adequate suppression of T2 inflammation with currently available therapies.
P-181 Outcomes of neoadjuvant and/or adjuvant treatment vs surgical resection alone for patients with cholangiocarcinoma: An inverse probability of treatment weighting with predictive nomogram
Authors: H. Hassan, W. Vanessa, T. Zemla, J. Yin, K. Prasai, A. Abdellatief, R. Katta, N. Tran, A. Mahipal
Journal: Annals of Oncology (2022)
P-236 Time intervals from presentation to treatment of colorectal cancer in Libya: A study of cases referred to medical oncology at Tripoli University Hospital, Tripoli, Libya in 2021
Authors: I. Siala, A. Abushaala, M. Grain, A. Almuqqudamii, N. Alzaroug, S. Abdulrahman, F. Abudeeb
Journal: Annals of Oncology (2022)
SO-2 Comparison of resected vs non-resected patients with unresectable locally advanced pancreatic cancer (LAPC) receiving P-32 microparticles with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy in the PanCO study
Authors: P. Ross, M. Nikfarjam, N. Nguyen, M. Aghmesheh, D. Burnett, H. Wasan, D. Turner, D. Croagh
Journal: Annals of Oncology (2022)
SO-29 Dihydropyrimidine dehydrogenase (DPD) genotype and phenotype among Danish cancer patients: Prevalence and correlation between DPYD-genotype mutations and P-uracil concentrations
Authors: N. Paulsen, M. Ewertz, T. Bergmann, H. Holm, S. Feddersen, P. Fruekilde, F. Vojdeman, H. Nielsen, C. Qvortrup, P. Plomgaard, B. Bertelsen, C. Rossing, S. Andersen, E. Greibe, E. Hoffmann-Lücke, A. Ramlov, C. Nielsen, I. Lolas, P. Bøttger, M. Bergmann, P. Pfeiffer, P. Damkier
Journal: Annals of Oncology (2022)
P-258 Chemoimmunotherapy in the context of total neoadjuvant therapy (TNT) in patients with locally advanced rectal cancer
Authors: A. Shamseddine, R. Turfa, C. Elias, J. Kattan, D. Mukherji, S. Temraz, K. Alqasem, R. Amarin, T. Al Awabdeh, S. Deeba, I. Mohamad, F. Daoud, M. Al Masri, A. Dabous, A. Hushki, O. Jaber, M. Charafeddine, M. Al Darazi, Y. Zeidan, F. Geara
Journal: Annals of Oncology (2022)
P-142 Inflammatory biomarkers in patients with advanced pancreatic adenocarcinoma undergoing first-line chemotherapy with nab-paclitaxel and gemcitabine: A single-center study
Authors: A. Ioannou, G. Papaxoinis, P. Gouveris, D. Zouki, V. Kardara, S. Ioannou, K. Exarchos, V. Adamou, I. Bitsas, G. Karianakis, G. Koronakis, N. Stavrou, S. Demiri
Journal: Annals of Oncology (2022)
Motor Network Reorganization Induced in Chronic Stroke Patients with the Use of a Contralesionally-Controlled Brain Computer Interface
Authors: Joseph B. Humphries, Daniela J. S. Mattos, Jerrel Rutlin, Andy G. S. Daniel, Kathleen Rybczynski, Theresa Notestine, Joshua S. Shimony, Harold Burton, Alexandre Carter, Eric C. Leuthardt
Journal: Brain-Computer Interfaces (2022)

Upper extremity weakness in chronic stroke remains a problem not fully addressed by current therapies. Brain–computer interfaces (BCIs) engaging the unaffected hemisphere are a promising therapy that are entering clinical application, but the mechanism underlying recovery is not well understood. We used resting state functional MRI to assess the impact a contralesionally driven EEG BCI therapy had on motor system functional organization. Patients used a therapeutic BCI for 12 weeks at home. We acquired resting-state fMRI scans and motor function data before and after the therapy period. Changes in functional connectivity (FC) strength between motor network regions of interest (ROIs) and the topographic extent of FC to specific ROIs were analyzed. Most patients achieved clinically significant improvement. Motor FC strength and topographic extent decreased following BCI therapy. Motor recovery correlated with reductions in motor FC strength across the entire motor network. These findings suggest BCI-mediated interventions may reverse pathologic strengthening of dysfunctional network interactions.
P-120 Front-line treatment of locally advanced pancreatic adenocarcinoma with tumour treating fields concomitant with gemcitabine and nab-paclitaxel: The phase 3 PANOVA-3 study
Authors: V. Picozzi, T. Macarulla, P. Philip, C. Becerra, T. Dragovich
Journal: Annals of Oncology (2022)

Tumour Treating Fields (TTFields) are a novel, locoregional antimitotic treatment modality approved for glioblastoma and malignant pleural mesothelioma. Continuous, non-invasive low intensity, intermediate frequency (150–200 kHz) alternating electric fields are delivered to the tumour via arrays placed on the skin. TTFields (150 kHz), with or without chemotherapy, induced antiproliferative and anticlonogenic activity on pancreatic cancer cell lines in vitro. The phase 2 PANOVA study (NCT01971281) demonstrated that the combination of TTFields with nab-paclitaxel and gemcitabine (GnP) is well-tolerated, with promising efficacy in both metastatic and locally advanced pancreatic adenocarcinoma (LAPC). These data indicated that TTFields with GnP warrant phase 3 evaluation. PANOVA-3 (NCT03377491) is a prospective, randomised, phase 3 trial designed to investigate the efficacy and safety of TTFields concomitant with GnP in patients with LAPC. The planned enrolment is 556 patients. Eligibility criteria include unresectable LAPC (per National Comprehensive Cancer Network guidelines), Eastern Cooperative Oncology Group performance status of 0–2, and no prior progression or treatment. Patients will be stratified by performance status and geographical region, and randomly assigned 1:1 to TTFields plus GnP or GnP alone. Based on a recent protocol amendment, a smaller and lighter-weight (reduced from 6 to 2.7 lbs) TTFields device will be used. Standard doses of nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) will be administered on days 1, 8, and 15 of a 28-day cycle. TTFields (150 kHz) will be delivered ≥ 18 h/day until local disease progression per Response Evaluation Criteria in Solid Tumours v1.1. Follow-up will be performed every 4 weeks and a computed tomography scan of the chest and abdomen every 8 weeks. After local disease progression, patients will be followed every month until death. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival (PFS), local PFS, objective response rate, 1-year survival rate, pain- and puncture-free survival rate, rate of resectability, quality of life, and toxicity. The sample size was estimated per log-rank test comparing time to event in patients treated with TTFields plus GnP with published clinical trial data on patients treated with GnP alone. PANOVA-3 is designed to detect a hazard ratio of 0.75 in OS. Type I error is set to 0.05 (2-sided) and power to 80%. The trial is currently recruiting at 110 sites in Australia, Austria, Belgium, Canada, China, Croatia, Czech Republic, France, Germany, Hong Kong, Hungary, Israel, Italy, Poland, Spain, Switzerland, and USA. The DMC last reviewed the trial in August 2021 and suggested that the trial continue as planned. NCT03377491. Novocure Ltd. Novocure Ltd.
Comparison of 18F-MFBG and 68Ga-DOTATATE PET/CT in the Imaging of Metastatic Paraganglioma and Pheochromocytoma
Authors: Maoxue Deng, Qiaoqiao Shu, Mei Hu, Yue Chen, Liang Cai
Journal: Clinical Nuclear Medicine (2022)

Two men with metastatic paraganglioma/pheochromocytoma underwent PET/CT examination in our hospital to understand the treatment effect and progression of the disease. Both patients had previously been treated with 131 I-MIBG, and at this evaluation, both of them underwent 68 Ga-DOTATATE and 18 F-MFBG PET/CT. The 68 Ga-DOTATATE PET/CT showed more metastases in the images of these 2 patients. This case highlighted that 68 Ga-DOTATATE PET/CT is superior to 18 F-MFBG PET/CT in detecting metastases from paraganglioma and pheochromocytoma in these 2 patients.
LBA O-10 First-line panitumumab versus bevacizumab in combination with mFOLFOX6 for RAS wild-type metastatic colorectal cancer: PARADIGM trial results
Authors: K. Muro, J. Watanabe, K. Shitara, K. Yamazaki, H. Ohori, M. Shiozawa, H. Yasui, E. Oki, T. Sato, T. Naitoh, Y. Komatsu, T. Kato, M. Hihara, J. Soeda, K. Yamamoto, K. Akagi, A. Ochiai, H. Uetake, T. Yoshino
Journal: Annals of Oncology (2022)